The urinary excretion of orally administered pteroyl-l-glutamic acid by the rat

1. The urinary excretion of folates after oral administration of [2-(14)C]pteroyl-l-glutamic acid was studied by assaying the radioactivity in the urine and in materials purified and characterized by t.l.c. 2. Radioactivity excreted was 6.8, 5.9 and 30.7% of the oral dose in the first 24h after doses of 3.1, 32 and 320mug/kg respectively. 3. Extensive decomposition of urinary folates to pteroyl-l-glutamic acid was prevented by antioxidants or collection of urine frozen. 4. At the three dosages, two major and one minor radioactive compounds were isolated. One of the major metabolites was 5-methyltetrahydropteroylglutamic acid. The others were unidentified but were not pteroylglutamic acid, 7,8-dihydro-, 5,6,7,8-tetrahydro-, 5- or 10-formyl-tetrahydro-, 5,10-methylidyne-tetrahydro-, 5-formimidoyl-tetrahydro-, 5,10-methylene-tetrahydro-, 5-methyltetrahydro-pteroylglutamic acid, nor any decomposition products of these compounds formed during isolation. Labelled unconjugated pteridines were absent. 5. Labelled pteroyl-l-glutamic acid was displaced by oral administration of unlabelled pteroyl-l-glutamic acid (1.6mg/kg) when given 3.5h after, but not when given 24h after the labelled dose. 6. The results show that orally administered [2-(14)C]pteroyl-l-glutamic acid is absorbed without metabolism and is then metabolized into naturally occurring tetrahydro-folates. 7. These findings are discussed with reference to previous work.     

Effect of centrally administered gamma-aminobutyric acid on metabolic function

gamma-Aminobutyric acid (GABA) content of the brain increases during hypoxia and hypercapnia and GABA by itself is a central ventilatory depressant and may depress metabolism as well. Therefore the effect of centrally administered GABA by ventriculocisternal perfusion on O2 consumption (VO2) and CO2 production (VCO2) was studied in pentobarbital-anesthetized dogs. GABA (30 mM) in mock cerebrospinal fluid (CSF) was perfused for 15 min at the rate of 1.0 ml/min followed by perfusion with mock CSF alone. Body temperature, perfusion pressure, and CSF pH were kept constant. Minute ventilation (VE) was kept constant mechanically. Under these conditions, VO2, VCO2, alveolar ventilation (VA), and relative pulmonary dead space volume (VD/VT) were measured. During perfusion with 30 mM GABA, mean VO2 (+/- SE) decreased from 96.5 +/- 3.3 to 81.9 +/- 5.1 ml/min, VCO2 from 72.1 +/- 3.8 to 60.7 +/- 3.0 ml/min, and VA from 1.7 +/- 0.1 to 1.3 +/- 0.1 l/min. VD/VT increased from 0.55 +/- 0.02 to 0.65 +/- 0.01. Perfusion with mock CSF alone restored these parameters to initial levels within 15 min. We conclude that centrally administered GABA depresses VO2 and VCO2. This reduction in metabolic function is independent of the central modulatory effects of GABA on respiration.     

5-Caffeoylquinic acid and caffeic acid orally administered suppress P-selectin expression on mouse platelets

Caffeic acid and 5-caffeoylquinic acid are naturally occurring phenolic acid and its quinic acid ester found in plants. In this article, potential effects of 5-caffeoylquinic acid and caffeic acid on P-selectin expression were investigated due to its significant involvement in platelet activation. First, the effects of 5-caffeoylquinic acid and caffeic acid on cyclooxygenase (COX) enzymes were determined due to their profound involvement in regulating P-selectin expression on platelets. At the concentration of 0.05 microM, 5-caffeoylquinic acid and caffeic acid were both able to inhibit COX-I enzyme activity by 60% (P<.013) and 57% (P<.017), respectively. At the same concentration, 5-caffeoylquinic acid and caffeic acid were also able to inhibit COX-II enzyme activity by 59% (P<.012) and 56% (P<.015), respectively. As expected, 5-caffeoylquinic acid and caffeic acid were correspondingly able to inhibit P-selectin expression on the platelets by 33% (P<.011) and 35% (P<.018), at the concentration of 0.05 microM. In animal studies, 5-caffeoylquinic acid and caffeic acid orally administered to mice were detected as intact forms in the plasma. Also, P-selectin expression was respectively reduced by 21% (P<.016) and 44% (P<.019) in the plasma samples from mice orally administered 5-caffeoylquinic acid (400 microg per 30 g body weight) and caffeic acid (50 microg per 30 g body weight). These data suggest that both 5-caffeoylquinic acid and caffeic acid orally administered can be absorbed and suppress P-selectin expression on mouse platelets.     

Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat

Ghrelin is a gut peptide that is secreted from the stomach and stimulates food intake. There are ghrelin receptors throughout the gut and intracerebroventricular ghrelin has been shown to increase gastric acid secretion. The aim of the present study was to examine the effects of peripherally administered ghrelin on gastric emptying of a non-nutrient and nutrient liquid, as well as, basal and pentagastrin-stimulated gastric acid secretion in awake rats. In addition, gastric contractility was studied in vitro. Rats equipped with a gastric fistula were subjected to an intravenous infusion of ghrelin (10-500 pmol kg(-1) min(-1)) during saline or pentagastrin (90 pmol kg(-1) min(-1)) infusion. After administration of polyethylene glycol (PEG) 4000 with 51Cr as radioactive marker, or a liquid nutrient with (51)Cr, gastric retention was measured after a 20-min infusion of ghrelin (500 pmol kg(-1) min(-1)). In vitro isometric contractions of segments of rat gastric fundus were studied (10(-9) to 10(-6) M). Ghrelin had no effect on basal acid secretion, but at 500 pmol kg(-1) min(-1) ghrelin significantly decreased pentagastrin-stimulated acid secretion. Ghrelin had no effect on gastric emptying of the nutrient liquid, but significantly increased gastric emptying of the non-nutrient liquid. Ghrelin contracted fundus muscle strips dose-dependently (pD2 of 6.93+/-0.7). Ghrelin IV decreased plasma orexin A concentrations and increased plasma somatostatin concentrations. Plasma gastrin concentrations were unchanged during ghrelin infusion. Thus, ghrelin seems to not only effect food intake but also gastric motor and secretory function indicating a multifunctional role for ghrelin in energy homeostasis.     

Peripheral mechanisms involved in the pressor and bradycardic effects of centrally administered arachidonic acid

In the current study, we aimed to determine the cardiovascular effects of arachidonic acid and peripheral mechanisms mediated these effects in normotensive conscious rats. Studies were performed in male Sprague Dawley rats. Arachidonic acid was injected intracerebroventricularly (i.c.v.) at the doses of 75, 150 or 300 microg and it caused dose- and time-dependent increase in mean arterial pressure and decrease in heart rate in normal conditions. Maximal effects were observed 10 min after 150 and 300 microg dose of arachidonic acid and lasted within 30 min. In order to evaluate the role of main peripheral hormonal mechanisms in those cardiovascular effects, plasma adrenaline, noradrenaline, vasopressin levels and renin activity were measured after arachidonic acid (150 microg; i.c.v.) injection. Centrally injected arachidonic acid increased plasma levels of all these hormones and renin activity. Intravenous pretreatments with prazosin (0.5 mg/kg), an alpha1 adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2-Arg8]-vasopressin (10 microg/kg), a vasopressin V1 receptor antagonist, or saralasin (250 microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to arachidonic acid (150 microg; i.c.v.) while combined administration of these three antagonists completely abolished the effect. Moreover, both individual and combined antagonist pretreatments fully blocked the bradycardic effect of arachidonic acid. In conclusion, our findings show that centrally administered arachidonic acid increases mean arterial pressure and decreases heart rate in normotensive conscious rats and the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity appear to mediate the cardiovascular effects of the drug.     

Aspartic acid administered neonatally affects ventilation of male and female rats differently

In this study ventilation was evaluated in 12-mo-old male and female rats who had received large doses of aspartic acid neonatally. Rats of both sexes treated with aspartic acid were obese, stunted, and exhibited hypogonadism. Although metabolic rates of the aspartic acid-treated rats were not different compared with sex-matched controls, ventilatory patterns were different. Aspartic acid-treated females breathed with a smaller tidal volume (VT), higher frequency (f), and similar minute ventilation (VE) compared with control females. This pattern is commonly observed in many patients who are obese. The aspartic acid-treated females responded to hypercapnic and hypoxic challenges by increasing f more than VT. Tissue pocket gases (PCO2 and PO2) of aspartic acid-treated females were normal. In contrast, aspartic acid-treated males hypoventilated compared with control males. Tissue pocket gas values suggested that aspartic acid-treated males were hypoxemic and hypercapnic. Moreover, the response of aspartic acid-treated males to hypercapnia was parallel to but was less than that of control male rats. The ventilatory response of aspartic acid-treated male rats to hypoxia was blunted. This study has shown that neonatal administration of aspartic acid causes a decreased ventilation and blunted response to hypoxia in adult male but not female rats.     

Effect of transdermally administered hyoscine methobromide on nocturnal acid secretion in patients with duodenal ulcer.

Use of anticholinergic drugs in treatment of duodenal ulcers is limited by the side effects of widespread parasympathetic blockade evoked by usual therapeutic doses. A study was conducted into the effectiveness of transdermal delivery of hyoscine methobromide using a new system which releases the drug into the circulation at a controlled rate. In six patients whose duodenal ulcer had healed secretion of acid was measured over two nights, the first on placebo and the second on hyoscine methobromide. All patients responded to the active drug and showed a significant inhibition of acid secretion. Four subjects complained of a dry mouth after overnight treatment with hyoscine methobromide; no other side effects were reported. Transdermal delivery of anticholinergic drugs may be useful in maintenance treatment of duodenal ulcers and further clinical tests are indicated.     

Intranasally administered phenylephrine and blood pressure.

The possibility that intranasally administered phenylephrine might cause systemic vasoconstriction and an important increase in blood pressure if administered to susceptible individuals in higher doses was investigated in two groups potentially at high risk: 12 patients with chronic nasal congestion whose blood pressure was normal and 14 patients with hypertension receiving the beta-blocker metoprolol. On two separate days increasing doses (0.5 to 4 mg) of phenylephrine or a placebo of identical appearance were instilled into the nostrils at hourly intervals. The blood pressure and the heart rate were recorded every 10 minutes. The total amount of phenylephrine administered (7.5 to 15 mg) was 4 to 30 times the manufacturer''s recommended dose. No significant changes in blood pressure or heart rate occurred in either group after the instillation of phenylephrine.     

Utilization of metal ions administered as labelled salts of phosphatidic acid

Phosphatidic acid is used in food technology as an emulsifier. Simultaneously, it can serve as a carrier for different biologically important metal ions. This paper concerns the stability of phosphatidic acid salts in body fluids and the incorporation and distribution of metal ions into the organs of experimental animals. It was found that the absorption of metals, released from salts of phosphatidic acid after administration, is comparable with the absorption of easily dissociable inorganic salts.     

Prenatal development of acid beta-glycosidases in the rat liver, effect of triiodothyronine or cortisone administered to pregnant rats.

We have found that acid beta-galactosidase, beta-glucuronidase and N-acetyl-beta-glucosaminidase in the rat fetal liver increase during the last week of pregnancy. These enzyme activities were influenced by treatment of pregnant rats (daily from day 16) with L-tri-iodothyronine (20 or 50 microgram/100 gm b.w.) or cortisone acetate (10 or 50 mg/100 gm b.w.) as studied in their fetuses obtained on day 22 by caesarian section.